Functions of O-glycans: In collaboration with the Ten Hagen lab (NIH), Stasia Anderson, Daryl Despres and M Starost (NIH), we have continued studies on the cardiac phenotypes resulting from the deletion of GalNAc-T1. We have found that the heart valves are markedly enlarged in the affected hearts. We are analyzing the underlying molecular cause(s) for this phenotype. Tom Beres in collaboration with the Angerer lab (NIH), examined the roles of GalNAc-Ts and mucin-type O-glycosylation during embryonic development of the sea urchin, S. purpuratus. Two phenotypes are being characterized in morphants in which GalNAc-T7 expression is ablated. One phenotype involves the loss of muscle, and the other, embryos lack both the ciliated band (cells with cilia that sweep food into the mouth) and the network of nerves normally present in this region. Raul Rojas, using confocal microscopy, has studied the targeting signals in GalNAc-Ts that direct these enzymes from the endoplasmic reticulum to the Golgi and then retain them in the Golgi. We have a series of collaborations with investigators around the world to assess/phenotype various mouse models in which the expression of specific GalNAcTs have been ablated. This includes work with A.G. Holleboom and J.A. Kuivenhoven on the role of GalNAc-T2 on the control of lipids, and with Q. Zheng on the function of GalNAc-T2 on otitis media. Mechanisms of GalNAcT function: We are collaborating with L. Masgrau to use the hybrid QM/MM (quantum mechanics/molecular mechanics) approach to study the retaining mechanism used by GalNAc-Ts in forming O-glycans.